Effect of feed supplementation with kynurenic acid on the morphology of the liver, kidney and gills in rainbow trout (Oncorhynchus mykiss Walbaum, 1792), healthy and experimentally infected with Yersinia ruckeri

Abstract

Kynurenic acid (KYNA) is an endogenous substance produced on the kynurenine pathway which is primarily known for its neuroactive properties. Recently, it has been proven that KYNA is a selective ligand for G protein-coupled receptor (GPR 35), presented on immunocompetent cells such as T lymphocytes. This opens up new possibilities of its application as an immunostimulating substance in aquaculture. Thus far, no histopathological investigations in fish have been completed to evaluate influence of KYNA supplementation in feed. This study has been undertaken to determine the effect of feed supplementation with KYNA (2.5, 25, 250 mg kg of feed) for 28 days on the liver, gills and kidney in healthy fish and experimentally infected with Yersinia ruckeri. In a control group were observed a fatty liver, which is natural for this fish species in the autumn and winter season. As the dose of the supplement was increased, the fat liver changed, it decreased or completely disappeared. Additionally, inflammatory changes occurred in all the analysed organs, and their intensification was dose dependent. In the fish experimentally infected, KYNA caused aggravation of the signs in the liver, kidneys and gills, and the effect was dose dependent. The results implicate that KYNA may be a stressor for fish.

Analysis of the Long-Lived Responses Induced by Immunostimulants and Their Effects on a Viral Infection in Zebrafish (Danio rerio)

“…The intermediates of the kynurenine pathway, due to their toxic potential, may cause tissue damage and, as a consequence, generate higher stress, which can in turn interfere with the immune response to minimize tissue damage. It was recently observed that feed supplementation with kynurenic acid (KYNA) in rainbow trout had a toxic/stress-inducing effect, and this deleterious effect was related to the dose of KYNA ( 65 ). This pathological status was manifested during a subsequent infection with Yersinia ruckeri , with a higher mortality rate in animals that were administered a higher concentration of KYNA ( 65 ).…”

“…It was recently observed that feed supplementation with kynurenic acid (KYNA) in rainbow trout had a toxic/stress-inducing effect, and this deleterious effect was related to the dose of KYNA ( 65 ). This pathological status was manifested during a subsequent infection with Yersinia ruckeri , with a higher mortality rate in animals that were administered a higher concentration of KYNA ( 65 ). On the other hand, kynurenic acid is an endogenous agonist of gpr35 (which was the second most upregulated gene in β-glucan-stimulated zebrafish in the absence of infection), and its activation increases FAO and induces an anti-inflammatory state ( 66 , 67 ).…”

Kynurenic Acid: The Janus-Faced Role of an Immunomodulatory Tryptophan Metabolite and Its Link to Pathological Conditions

“…In this context, the microbial-mediated KYNA catabolism, known so far from Pseudomonas and Aerococcus ( 60 , 61 ), might be relevant. Interestingly, feed supplementation with very high amounts of KYNA might have a toxic/stress-inducing effect in rainbow trout ( 161 ). Hence, further studies are necessary to evaluate if a supplementation of KYNA is beneficial or detrimental to human health.…”

Kynurenic Acid and Its Analogs Are Beneficial Physiologic Attenuators in Bdelloid Rotifers

“…KYNA has a key role in numerous biological species and their environment. The natural abundance of this biomolecule is essential in plants [19], in animal feed [20], in amphibians as pheromones [21] and moreover in fish as lymphocyte-activators [22] with potential aggravating properties [23].…”